1. Field of the Invention
The present invention relates to an adhesive composition, particularly relates to a cyanoacrylate adhesive composition for wound or surgical incision closure and a method for making the same.
2. The Prior Arts
For treatment of small wounds, in general, the anti-inflammatory and anti-microbial drugs are applied so that the wound is gradually closed and healed by natural tissue regrowth. The drugs used here are intended for preventing bacterial infection and easing the pain. However, when the wound is large and deep, rejoining adjacent skins around the wound by sutures is a suitable treatment method to promote prompt wounds healing. Compared to the suturing, the tissue adhesive is currently becoming more popular for wound closure because of its unique properties.
The so-called tissue adhesive is like a glue. When it is used for wound closure, the liquid adhesive is coated on the skin surface adjacent to the wound. Through a curing reaction, the tissue adhesive is solidified and the skins adjacent to the wound can be bonded together by the adhesive, so that the aforementioned wound closure is achieved. Due to the proliferation of epidermal tissue, the cured adhesive would slough off with epidermal cells after about 5-10 days. In some case, the tissue adhesive could be absorbed by the tissue after a period of time. In comparison with the disadvantages of longer operation time and pains associated with the traditional skin suture surgery, utilizing the tissue adhesive for wound closure has the benefits of easy to use, time saving, less pain, and better cosmetic results. As a result, it is the preferred option either for common wound treatment or being an auxiliary treatment for a deep wound. In addition, the tissue adhesive can also be employed to stop the bleeding in ulcer, as an adhesive between the tissue or binding implants to the tissues, etc.
A preferred tissue adhesive has the following characteristics: (1) having sufficient viscosity so that it can be retained on/near the wound and doesn't flow to unexpected location, and it can cure in a short period of time to close the wound promptly; (2) can bond to tissue in the presence of water and having sufficient binding strength, tensile strength and toughness; (3) having excellent biocompatibility, nontoxic and not causing immune responses; (4) being biodegradable; (5) can be used as a scaffold for cell or tissue growth and thus promote healing.
Available tissue adhesives can be divided into three main categories: (1) cyanoacrylate adhesives; (2) fibrin glues; and (3) crosslinked protein glues. Among those, fibrin glues are prepared from animal or human blood. Even though they possess good biocompatibility, there are risks of viral infection. Further, the binding force of fibrin glues is relatively weak with about 3-4 N/cm2, which is a disadvantage for tissue adhesive. As for the crosslinked protein glues, although they also have good biocompatibility and biodegradability, the risk of viral infection is the same as fibrin glues. Comparatively, cyanoacrylate adhesives can polymerize rapidly and bond wounds in a few minutes with excellent adhesive performance; thereby they have outstanding hemostasia performance and are able to treat large wounds.
Cyanoacrylate adhesives are generally applied in monomeric form for wound closure. The cyanoacrylate monomers normally start anionic polymerization in the presence of water on the skin surface forming the desired adhesive bond with the skin. However, the monomeric form of cyanoacrylate has a very low inherent viscosity which can result in the flow of the adhesive into undesirable areas or into the wound. Other than causing damage to the adjacent tissue, this may affect the wound healing as well. In order to obtain a cyanoacrylate adhesive composition with a higher viscosity, different thickening agents, e.g. polycyanoacrylate, have been added to the adhesive composition. Polycyanoacrylate is generally prepared by initiating polymerization of cyanoacrylate monomers with bicarbonate or the like as an accelerator/initiator. Then a cleaning or neutralization step with an acid is usually required to remove the excess bicarbonate or the like. However, residual accelerators in polycyanoacrylate would cause premature polymerization of the adhesive (containing cyanoacrylate monomers) when the polycyanoacrylate is added therein, and consequently resulting in reduction of bonding strength and the adhesive's performance for wound closure.